While bone fractures usually heal successfully, a significant number, approaching 300,000 fractures per year in the US, heal slowly or do not heal at all. In addition to these fractures, in the US each year there are approximately 200,000 spinal fusions for lower back pain. Spinal fusions consume over half of all available bone graft substitutes including human bone derived from cadavers. Importantly, the available growth factors used to treat fractures and fusions are extremely expensive. Using harvested bone from the patient is associated with increased morbidity, and the delivery of both tissue grafts and growth factors require open surgery, which can increase risks of medical complications to the patient. Because of these limitations and expense of current practice, there is a tremendous need for a cost-effective product that can be injected directly into bone repair sites to accelerate healing. The goal of our study is to develop a cost-effective, convenient product for healing bone that consists of a peptide growth factor, HomoSer3-AIII, derived from angiotensin, in an injectable gel, Oxiplex(r), that consists of two biocompatible synthetic polymers. The aims are: 1). to select from three formulations, based upon handling, biocompatibility, efficacy on bone healing, and peptide stability an injectable system for the percutaneous delivery of HomoSer3-AIII to the site of bone injury using Oxiplex technology. 2). to determine the efficacy of HomoSer3-AIII on bone healing delivered using the selected injectable system in two animal models for bone healing. The probability of this project being successful is high because we have already shown that MSC grown in culture in the presence of All are capable of expressing characteristics of bone cells (alkaline phosphatase). These data support the hypothesis that angiotensin peptides can accelerate the growth of MSC while maintaining their ability to differentiate into bone. We also have shown that Oxiplex/SP, (a formulation similar to the one to be developed here and currently marketed for reduction of peridural fibrosis after spinal surgery in Europe), accelerated the formation of bone in a rat tibia repair model, and with the addition of HomoSer3-AIII to the gel, there was substantial increased bone deposition, remodeling and repair. If this project and future phase II SBIR development studies leads to a cost-effective formulation for bone healing, FzioMed will manufacture, market and distribute this product to orthopedic surgeons.